인진약침이 고지방식이유도 비만 ICR Mice에서 항비만 및 대사이상 개선에 미치는 영향 Artemisia capillaries Herbal Acupuncture Improves Metabolic Abnormalities in High Fat Diet-induced Obese ICR Mice원문보기
목적 : 인진약침이 고지방식이로 유발된 비만 ICR mice에서 비만 및 동반 대사이상에 미치는 효과와 그 기전을 연구하고자 한다. 방법 : 인진약침의 비만 예방효과를 검증하기 위하여, 4주간 고지방식이를 급여하면서 150mg/kg 또는 300mg/kg의 인진약침을 양측 비수($BL_{20}$)에 교대로 매일 피하에 시술하였다. 또한 인진약침의 비만 치료효과를 검증하기 위하여, 4주간 고지방식이를 급여한 비만 ICR mice에 추가 4주간 고지방식이를 유지하면서 300 mg/kg 인진약침액과 vehicle control로써 등량의 distilled water를 양측 비수($BL_{20}$)에 교대로 매일 피하에 약침시술하였다. 인진약침의 항비만효과와 기전을 알아보기 위해, 체중, blood glucose, insulin, total cholesterol, triglyceride, non-esterified fatty acid (NEFA), AST, ALT levels 등 대사지표를 측정하고 부고환조직의 조직학적 관찰을 시행하였으며, AMPK activation과 adipocyte differentiation, fatty acid ${\beta}$-oxidation 및 thermogenesis와 관련된 gene expressions을 평가하였다. 결과 : 인진약침의 치료를 통하여 고지방식이 급여로 인한 체중의 증가가 억제되었을 뿐만 아니라, 비만 ICR mice의 체중을 감소시켰으며, glucose 및 lipid homeostasis를 개선시켰으며 지방조직의 증식을 억제하였다. AMPK의 phosphorylation과 CPT-1 및 UCP2의 발현을 증가시켰으며, PPAR-${\gamma}$, C/EBP${\alpha}$, aP2, LPL,FAS, SCD-1의 발현을 억제하였다. 결론 : 인진약침은 고지방식이 유도 동물모델에서 비만 및 동반 대사이상을 개선시키는 효과가 있으며, 이는 식이억제에 의한 2차적 효과라기 보다는 energy expenditure를 증가시키고, pre-adipocyte differentiation 및 proliferation을 억제하며, lipogenesis를 억제하고 lipolysis를 증가시키는 효과에 의한 것으로 사료된다.
목적 : 인진약침이 고지방식이로 유발된 비만 ICR mice에서 비만 및 동반 대사이상에 미치는 효과와 그 기전을 연구하고자 한다. 방법 : 인진약침의 비만 예방효과를 검증하기 위하여, 4주간 고지방식이를 급여하면서 150mg/kg 또는 300mg/kg의 인진약침을 양측 비수($BL_{20}$)에 교대로 매일 피하에 시술하였다. 또한 인진약침의 비만 치료효과를 검증하기 위하여, 4주간 고지방식이를 급여한 비만 ICR mice에 추가 4주간 고지방식이를 유지하면서 300 mg/kg 인진약침액과 vehicle control로써 등량의 distilled water를 양측 비수($BL_{20}$)에 교대로 매일 피하에 약침시술하였다. 인진약침의 항비만효과와 기전을 알아보기 위해, 체중, blood glucose, insulin, total cholesterol, triglyceride, non-esterified fatty acid (NEFA), AST, ALT levels 등 대사지표를 측정하고 부고환조직의 조직학적 관찰을 시행하였으며, AMPK activation과 adipocyte differentiation, fatty acid ${\beta}$-oxidation 및 thermogenesis와 관련된 gene expressions을 평가하였다. 결과 : 인진약침의 치료를 통하여 고지방식이 급여로 인한 체중의 증가가 억제되었을 뿐만 아니라, 비만 ICR mice의 체중을 감소시켰으며, glucose 및 lipid homeostasis를 개선시켰으며 지방조직의 증식을 억제하였다. AMPK의 phosphorylation과 CPT-1 및 UCP2의 발현을 증가시켰으며, PPAR-${\gamma}$, C/EBP${\alpha}$, aP2, LPL,FAS, SCD-1의 발현을 억제하였다. 결론 : 인진약침은 고지방식이 유도 동물모델에서 비만 및 동반 대사이상을 개선시키는 효과가 있으며, 이는 식이억제에 의한 2차적 효과라기 보다는 energy expenditure를 증가시키고, pre-adipocyte differentiation 및 proliferation을 억제하며, lipogenesis를 억제하고 lipolysis를 증가시키는 효과에 의한 것으로 사료된다.
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제안 방법
AC : high fat diet group treated with AC herbal acupuncture. Animals were subcutaneously injected daily into both Bisu (BL20) alternately with either distilled water as vehicle control or AC herbal acupuncture (150 mg/kg or 300 mg/kg) respectively for 4 weeks.
The acupuncture point is widely applied for the treatment of various conditions such as spleen deficiency syndrome, gastrointestinal disorders, abdominal mass, jaundice, ascites, edema, diabetes by spreading, regulating and nourishing spleen qi, and clearing dampness39). Animals were subcutaneously injected with 1.0ml syringe (26 gauge needle, Green Cross Medical Equipment, Korea) into both Bisu (BL20) everyday alternately with either AC herbal acupuncture (150 mg/kg or 300 mg/kg) or distilled water as vehicle control respectively for 4 weeks.
The care, maintenance and treatment of animals in these studies followed protocols approved by the Institutional Animal Ethics Committee of the Kyung Hee University. For prevention mode, mice were randomly divided into four groups: regular diet group (RD, D12450B; Research Diets, INC, New Brunswik, NJ, USA), high fat diet group (HFD, D12451; Research Diets, INC, New Brunswik, NJ, USA) with vehicle control, group fed HFD with 150 mg/kg of AC herbal acupuncture treatment (AC 150) and group fed HFD with 300 mg/kg of AC herbal acupuncture treatment (AC 300). For treatment mode, mice were fed with high fat diet for 4 weeks, and then 300 mg/kg of AC herbal acupuncture or distilled water as vehicle control was subcutaneously administered for additional 4 weeks with continuous high fat diet.
PCR was initiated a thermal cycler programmed at 95℃ for 5 min, 95℃ for 30 sec, 57℃ for 30 sec, 72℃ for 30 sec, and amplified for 30 cycles. The RT-PCR products were electrophoresed on 1% agarose gels and visualized by 0.5 ㎍/ml ethidium bromide staining and scanning densitometry was performed with I-MAX Gel Image analysis system (Core-Bio, Seoul, Korea). β-actin was amplified as a control gene.
대상 데이터
Five-week old ICR mice were purchased from Orient Bio (Seoul, Korea). All animals were acclimatized to the laboratory environment for 1 week before the experiment.
데이터처리
Results were expressed as mean±S.E.M and differences between groups were analyzed using Student’s t-test.
이론/모형
Korea). Plasma NEFA levels were determined using enzymatic colorimetric method (Eiken, Tokyo, Japan). Plasma AST and ALT levels were determined using commercially available kit (Stanbio, Boerne, Texas, USA).
At the end of the experimental period, the blood samples were collected and the levels of plasma glucose, insulin, triglyceride (TG), total cholesterol (TC), non-esterified fatty acid (NEFA), AST and ALT levels were measured. Plasma glucose concentrations were determined using the glucose oxidase method (Asan pharmaceutical Co, Korea). Plasma insulin concentrations were determined using a mouse insulin enzyme immunoassay kit (Gunma, Japan).
성능/효과
001) in AC 300 group compared to the HFD control group. As shown in Table 5, NEFA levels of AC herbal acupuncture groups were also markedly reduced compared to the HFD control group, by 26.5% in AC 150 and 49.6% in AC 300 group. While total cholesterol level in the HFD control group was increased by 26% compared to RD group, cholesterol levels in AC 150 and AC 300 groups were decreased by 14.
001) compared to the HFD control group. As shown in Table 7, NEFA, cholesterol, TG, AST and ALT levels in AC 300 group were all markedly reduced by 58.1%, 57.6%, 58.7%, 79.3% and 64.5%, respectively, compared to the HFD control group.
At the end of the experimental period, the blood samples were collected and the levels of plasma glucose, insulin, triglyceride (TG), total cholesterol (TC), non-esterified fatty acid (NEFA), AST and ALT levels were measured. Plasma glucose concentrations were determined using the glucose oxidase method (Asan pharmaceutical Co, Korea).
Similar to the results in prevention mode experiment, 300 mg/kg of AC herbal acupuncture significantly phosphorylated AMPK and ACC, and also enhanced gene expression responsible for fatty acid β-oxidation and thermogenesis, CPT-1 and UCP 2, respectively, when compared to those in the HFD control group (Fig. 6).
AC herbal acupuncture exerted beneficial effects on glucose and lipid homeostasis that were not secondary to its ability to decrease food intake but its specific effects on fatty acid β-oxidation, adipocyte differentiation and thermogenesis. Taken together, results obtained in this study suggest that antiobesity effect of AC herbal acupuncture can be arranged into three categories based on its distinct mechanisms; (1) increased energy expenditure, (2) decreased pre-adipocyte differentiation and proliferation, and (3) decreased lipogenesis and increased lipolysis.
3%, respectively compared to the HFD control group. To evaluate liver function, AST and ALT activities were compared between groups, and those levels in AC herbal acupuncture groups were both significantly lowered compared to those in the HFD control group.
6% in AC 300 group. While total cholesterol level in the HFD control group was increased by 26% compared to RD group, cholesterol levels in AC 150 and AC 300 groups were decreased by 14.5% and 18.2%, respectively. Triglyceride levels in AC 150 and AC 300 groups were also dose-dependently decreased by 33.
With decreased plasma glucose and insulin levels, insulin resistance index (HOMA-IR) values for AC herbal acupuncture groups were markedly decreased by 45.1% (p<0.01) in AC 150 and 64.3% (p<0.001) in AC 300 group compared to the HFD control group.
후속연구
Although the anti-obese activity of Artemisia capillaris observed from the present study could be attributed to many chemical constituents, such as scopoletin, capillarisin, 6, 7-dimethylesculetin, caffeic acid, chlorogenic acid, phenol, cresol, eugenol, and ethylphenol, previously reported in Artemisia capillaris53,54), future study to identify active component(s) and their dosage for obesity will be needed. Also, more research on the method of administering herbal acupuncture and selection of the acupuncture points of which will be applied is necessary.
And the preliminary experiments demonstrated that Artemisia capillaris exerted most effective anti-obese properties on adipocyte differentiation assay among 33 medicinal herbs tested. Although the anti-obese activity of Artemisia capillaris observed from the present study could be attributed to many chemical constituents, such as scopoletin, capillarisin, 6, 7-dimethylesculetin, caffeic acid, chlorogenic acid, phenol, cresol, eugenol, and ethylphenol, previously reported in Artemisia capillaris53,54), future study to identify active component(s) and their dosage for obesity will be needed. Also, more research on the method of administering herbal acupuncture and selection of the acupuncture points of which will be applied is necessary.
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